Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a constitutively active, secreted serine hydrolase enzyme encoded by the PLA2G7 gene that degrades a wide range of phospholipids through phospholipase A2 activity. This enzyme employs a nucleophilic serine residue to remove the sn2 acyl groups on phospholipids to release a free fatty acid and a lysophospholipid. Substrates of Lp-PLA2 include 1-alkyl-2-acetyl-sn-glycero-3-phosphocholines, also referred to as platelet-activating factor (PAF), and 1-acyl-2-acetyl-sn-glycero-3-phosphocholines, both of which initiate inflammatory signaling pathways. Lp-PLA2 is also capable of cleaving oxidized and truncated fatty acid acyl groups from phosphatidylcholine lipids found in oxidized LDL particles. This action produces pro-inflammatory lysophosphatidylcholines (LPC) and oxidized fatty acids. Because many of the substrates of Lp-PLA2 activate the platelet-activating factor receptor (PAF-R), a G-protein coupled receptor that mediates a wide range of physiological processes and diseases, including inflammation, asthma, autoimmunity, and tumor growth, Lp-PLA2 is thought to regulate these processes through its biochemical control of endogenous pools of PAF-R ligands. Therefore, Lp-PLA2 inhibition is a viable mechanism to target a number of diseases.